1. Field of Technology
The present invention generally relates to devices and methods for assessing the status of an individual's physical and/or mental performance, particularly as affected by such factors as disease, sleep deprivation, fatigue, excessive stress, alcohol or drugs. Still more particularly, the invention relates to such methods and devices which measure the speed of human visual perception.
2. Description of Related Art
Although medicine utilizes many measures of spatial vision, such as eye charts and perimetry, there are few ways to measure the temporal aspect of vision, i.e., the brain's speed of information processing. It is known that the visual brain collects information over windows of time (known as windows of integration). If two or more stimuli arrive within a single window of integration (usually less than 100 msec), they will be perceived as a single stimulus. For example, a child's toy known as a thaumatrope may have, for example, a picture of a bird on one side of a disc and a picture of a cage on the other. When the disc is wound up and spun quickly, so that both sides are seen in rapid alternation, the bird appears to be inside the cage. The two stimuli are alternating so rapidly that the visual system cannot distinguish them; they are seen as though they are simultaneously present. A good deal of data has been collected which shows that successive visual stimuli need to be presented within a small window of time (typically less than 100 msec) for the images to perceptually overlap.7 In other words, the visual brain collects information over windows of time. Under various circumstances, the duration of these windows can change.
Traditionally, the only methodologies for measuring the brain's speed of information processing use a flickering light. When the frequency of a flickering light is increased, the perception of flicker disappears at some point. The point where flickering perceptually fuses into steady light is called the “critical flicker fusion threshold” (CFFT). Flicker fusion measurements in medicine have been used for over a century48 for early diagnosis as well as for measurement of drug efficacy in the pharmaceutical industry.
The neurophysiology literature indicates that temporal measures involving flicker reflect something about central nervous system function. A number of studies point to CFFT being a reliable indicator of disease (such as Down's syndrome,33 Alzheimer's disease, and generalized cortical damage) as well as a measure of the effects of psychopharmaceuticals. Patients with dyslexia, an inability to read due to cortical dysfunction, have been reported to have impaired flicker detection.15 Flickering light is able to initiate neuronal activity in various parts of the visual system, from the retina to the brain cortex. It is clear from decades of study of disease, lesion and pharmacological agents that that the CFFT measurement relates to central nervous system (CNS) function rather than merely relating to the eyes or the optic pathways to the cortex. The central nature of flicker perception is supported by evidence that CFFT values are higher when measured with binocular vision rather than monocular vision53,54 and that exposure of only one eye to flicker alters the threshold sensitivity of the other eye.52 There is general agreement in the literature that CFFT is sensitive to the sedative and/or stimulant effect of CNS drugs.52,49,26,40 There is not, however, general agreement about what it measures: CNS sedation and arousal, CNS integration, psychomotor performance, information processing capacity and/or CNS impairment.12 
Measurements of CFFT have been used for the evaluation of psychoactive drugs,12 and are thought by some to be the most reliable method for measuring the effects of psychoactive drugs and central depressants.31 Detailed reviews of the application of CFFT in psychopharmacology have been published.52,49,25,26,30,21 In general, CFFT has been shown to distinguish between drugs, and even different dosages of the same drug, where other clinical rating scales are unable to do so. Some of the drugs in which CFFT has been used to assess their effects include anxiolytics,25,26,41,11,13,12 such as benzodiazepines, for which a reduction in threshold frequency has been observed because of their sedative effects. The measurement of CFFT is considered by some to be the most reliable technique available to assess a central depressant effect.31 
Another class of drugs in which CFFT has been used are the antidepressants. There are reports that CFFT is lower in elderly depressed patients compared with non-depressed elderly subjects.44 Further, the CFFT reportedly increases following treatment with anti-depressants.45 Tricyclic antidepressants can be grouped according to their sedative properties and effects of the CFFT.27,43 The general finding is that the tricyclics cause a greater reduction of threshold frequency compared to selective serotonin reuptake inhibitors (SSRIs).24 New antidepressants have also been distinguished in this way.50,26 
Still other types of prescribed medications have been reported in the literature to reduce CFFT, including beta-blockers,17 some cough suppressants,16 some antihistamines,51 anticonvulsants, and some antipsychotic drugs.40 Of the socially used drugs, alcohol is said to reduce CFFT,28 and nicotine is said to increase CFFT.46 The effect of caffeine remains equivocal.35 
Although it is still an open question whether there exists a good method for early detection of Alzheimer's disease before memory disturbance is apparent, CFFT has been suggested as one approach with potential advantages over other measures used for screening purposes.12 For diagnosing the onset of Alzheimer's disease, current methods of cognitive testing for dementia generally come too late. Neuroimaging is not practical for screening on a large scale, and currently available biochemical tests tend to identify Alzheimer's disease too late after onset. CFFT has been proposed as a non-invasive, easy to use and inexpensive means of screening people at high risk of developing Alzheimer's disease.
There have also been a number of investigations as to whether temporal measure is a signature of fatigue or arousal.38,19,21-23 A significant correlation between CFFT and self-rated alertness scores have been reported, and others have found that CFFT was significantly correlated with cortical alpha activity (a measure of arousal) measured by EEG. The correlation coefficients were relatively low, however, suggesting that CFFT is not simply a measure of sedation/arousal39 and it has been noted in the literature that the exact meaning of CFFT threshold changes is difficult to specify. CNS arousal/sedation is not a simple concept and may be the final outcome of many different processes. Furthermore, CNS drugs have many effects on brain function other than sedation/arousal, as illustrated by the effect of antidepressants. Although sedative antidepressants reportedly cause a reduction in CFFT scores in the early phase of treatment, CFFT scores increase as the depression resolves.45 This cannot be explained simply as “arousal,” since improvement is associated with many changes, including increased appetite, increased speed of thought processes, reduced psychomotor retardation, enhanced noradrenalin (NA) and serotonin/5-hydroxytryptamine (5-HT) functioning, restoration of biological rhythms and an ability to experience pleasure, to name just a few. Thus, although CFFT appears to reflect some aspect of CNS sedation/arousal, this concept is poorly defined and is the final outcome of a great many different processes.12 
Many studies have shown that the CFFT has high test/retest reliability.8,36,32,38,55,48,26,31 Thus, the CFFT is generally very stable for an individual subject, although it decreases slightly with increasing age. There is a slight degree of individual variability between subjects. Slight correlations have been reported between CFFT and eye color49 as well as intelligence,37 however, those correlations were low. The traditional method of flickering light has found that CFFT is affected by pupil size, being highest for large pupil sizes, which could be important if subjects are taking any medication that affects pupillary diameter. The stability of CFFTs allow changes in this measure to be potentially useful in diagnosis and psychopharmacology.
Existing data on CFFT indicates that long exposures to flickering light can alter the threshold, and CFFT is highest at the periphery of the retina and decreases towards the fovea. It is also known that CFFT increases with stimulus luminance and decreases with increasing luminance of the area surrounding the stimulus. CFFT also increases with the stimulus size.
Despite the increased knowledge that has been gained in recent years about the factors influencing CFFT, the basic measuring methodology has remained essentially unchanged. Available methods for measuring the CFFT typically require tens of minutes to conduct, necessitate training and expertise in administering the test, and are susceptible to falsification by the test subject.
Currently there are three primary methodologies for measuring CFFT. The first method is the “method of just noticeable differences.” According to this method the administrator of the test incrementally increases the frequency of a flickering light as a series of small steps. As the frequency increases, the flickering becomes more difficult to perceive and at some point fuses into an apparently solid light. The step at which this occurs is termed the “ascending threshold.” Then the test administrator does the same thing in reverse, starting from a high frequency and lowering it until the light appears to flicker again. This determines the “descending threshold” of the subject. There are no rigid guidelines regarding how many ascending and descending runs should be measured. In some tests a sufficient number of trials are performed until “the data seem stable,”14 which usually means averaging three or four ascending and descending thresholds.34,29 Conducting a CFFT test according to this method typically takes about 5 minutes.
In a second type of CFFT testing referred to as “the method of constant stimuli,” the test administrator chooses several flicker frequency stimulus values equally spaced over a range from rarely detected (well below the subject's perception threshold) to a flicker frequency that is nearly always detected by the subject (i.e., well above the threshold). These stimuli are then presented in random order. On each trial, the subject reports whether the stimulus was flickering (Yes/No response). The threshold is defined as the flicker frequency where subjects report flickering on 50% of the trials. This approach, while more exact than the first method, requires many trials, most of which are wasted because they are at the extremes of the testing range. This type of test takes up to ten times longer than the first method, making it generally unsuitable for use in clinical settings.
A similar third CFFT testing method is the “forced choice method,” in which the subject is presented with two stimuli, one steady and one flickering. The subject is forced to choose which is flickering. Again, this test requires a considerable number of trials to achieve the threshold, and thus many tens of minutes to administer.
There has been no clear evidence whether extreme fatigue, the kind that will cause drivers to crash vehicles, for example, has a clear temporal signature. Medical residents, pilots, soldiers, truck drivers and others frequently work long shifts which lead to sleep-deprivation. Excessive sleep deprivation leads to poor decision making which in turn may result in avoidable accidents3. Today, the available methods for assessing fitness for duty (FFD) measure brain activity using electroencephalography4,5 or ocular measures that require using eye trackers.6 As a practical matter, these methods have limited usefulness because they require expensive equipment, large time windows for testing, and are generally not well received by subjects.4 Other existing techniques utilize sensitive ocular measures, such as saccade velocity and speed of pupillary constriction to light.4 Such techniques are also impractical in most situations because they require expensive and sensitive equipment such as eye trackers. Eye trackers are not only expensive, but they also require a calibration period during which a subject is required to sit still with his head on a chin rest or bite bar. Still other techniques aimed at assessing fitness for duty utilize reaction time as a measure. For example, a picture appears on a screen, and a subject has to make a motor reaction to it (e.g., touch the screen) as quickly as possible. Such techniques are useful but somewhat cumbersome because they require equipment that will measure the speed and location of the touch. There is continuing interest in development of indicators of physical or mental impairment arising from drug effects, fatigue, stress, neurological disease and other conditions that impact central nervous system function.